Helminths are parasitic worms. They are the most common infectious agents of humans in developing countries and produce a global burden of disease that exceeds better-known conditions, including malaria and tuberculosis. As we discuss here, new insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies. At the same time, our understanding of the dynamics of the transmission of helminths and the mechanisms of the Th2-type immune responses that are induced by infection with these parasitic worms has increased markedly. Ultimately, these advances in molecular and medical helminth biology should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.

https://dm5migu4zj3pb.cloudfront.net/manuscripts/34000/34261/JCI0834261.v1.pdf

Helminth infections: the great neglected tropical diseases

Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

/pdf/the-genome-of-the-blood-fluke-schistosoma-mansoni-1btmt9bk5v.pdf

The genome of the blood fluke Schistosoma mansoni

Helminth immunoregulation: The role of parasite secreted proteins in modulating host immunity

Schistosomiasis, caused by trematode blood flukes of the genus Schistosoma, is recognized as the most important human helminth infection in terms of morbidity and mortality Infection follows direct contact with freshwater harboring free-swimming larval (cercaria) forms of the parasite Despite the existence of the highly effective antischistosome drug praziquantel (PZQ), schistosomiasis is spreading into new areas, and although it is the cornerstone of current control programs, PZQ chemotherapy does have limitations In particular, mass treatment does not prevent reinfection Furthermore, there is increasing concern about the development of parasite resistance to PZQ Consequently, vaccine strategies represent an essential component for the future control of schistosomiasis as an adjunct to chemotherapy An improved understanding of the immune response to schistosome infection, both in animal models and in humans, suggests that development of a vaccine may be possible This review considers aspects of antischistosome protective immunity that are important in the context of vaccine development The current status in the development of vaccines against the African (Schistosoma mansoni and S haematobium) and Asian (S japonicum) schistosomes is then discussed, as are new approaches that may improve the efficacy of available vaccines and aid in the identification of new targets for immune attack

https://cmr.asm.org/content/cmr/21/1/225.full.pdf

Current Status of Vaccines for Schistosomiasis

The eukaryotic nucleotide excision repair pathway.

Schistosoma mansoni is the primary causative agent of schistosomiasis, which affects 200 million individuals in 74 countries. We generated 163,000 expressed-sequence tags (ESTs) from normalized cDNA libraries from six selected developmental stages of the parasite, resulting in 31,000 assembled sequences and 92% sampling of an estimated 14,000 gene complement. By analyzing automated Gene Ontology assignments, we provide a detailed view of important S. mansoni biological systems, including characterization of metazoa-specific and eukarya-conserved genes. Phylogenetic analysis suggests an early divergence from other metazoa. The data set provides insights into the molecular mechanisms of tissue organization, development, signaling, sexual dimorphism, host interactions and immune evasion and identifies novel proteins to be investigated as vaccine candidates and potential drug targets.

/pdf/transcriptome-analysis-of-the-acoelomate-human-parasite-2a29kscb4m.pdf

Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni

Citrus sudden death (CSD) is a new disease that has killed approximately 1 million orange trees in Brazil. Here we report the identification of a new virus associated with the disease. RNAs isolated from CSD-affected and nonaffected trees were used to construct cDNA libraries. A set of viral sequences present exclusively in libraries of CSD-affected trees was used to obtain the complete genome sequence of the new virus. Phylogenetic analysis revealed that this virus is a new member of the genus Marafivirus. Antibodies raised against the putative viral coat proteins allowed detection of viral antigens of expected sizes in affected plants. Electron microscopy of purified virus confirmed the presence of typical isometric Marafivirus particles. The screening of 773 affected and nonaffected citrus trees for the presence of the virus showed a 99.7% correlation between disease symptoms and the presence of the virus. We also detected the virus in aphids feeding on affected trees. These results suggest that this virus is likely to be the causative agent of CSD. The virus was named Citrus sudden death-associated virus.

/pdf/identification-and-genomic-characterization-of-a-new-virus-31k5pptti6.pdf

Identification and Genomic Characterization of a New Virus (Tymoviridae Family) Associated with Citrus Sudden Death Disease

New ways for automatic detection of contaminats in EST projects.

Este trabalho apresenta uma nova metodologia para a determinacao computacional do organismo de origem de sequencias de DNA, implementada na forma de um programa chamado quest. O quest e baseado em dois principios: a extracao de informacoes intrinsecas a cada sequencia, chamadas de caracteristicas, e a extracao de diferentes tipos de caracteristicas e sua combinacao para se chegar a melhores resultados. Sao utilizados 7 diferentes programas como extratores de caracteristicas, alguns desenvolvidos por terceiros (Glimmer e ESTScan) e outros desenvolvidos pelo autor. As caracteristicas foram combinadas utilizando varios classificadores diferentes, variando desde uma soma simples ate os baseados em vetores de suporte. O quest requer sequencias para treinamento. Em comparacao com as abordagens baseadas em similaridade, as vantagens principais do quest estao no fornecimento de previsoes para as taxas de erro e na capacidade de lidar com sequencias sem similaridades signicativas em bancos de sequencias. O quest foi aplicado ao problema de determinar automaticamente contaminantes em projetos EST. Sao apresentados resultados de experimentos simulados e de um projeto EST real (o projeto EST de Schistosoma mansoni). Nos experimentos simulados foram atingidas taxas de falsos positivos mais falsos negativos de aproximadamente 10%. No projeto de S.mansoni o quest sugere que a contaminacao em sequencias supostamente legtimas poderia ser de pelo menos 6%. No teste com S.mansoni, o quest foi 10 vezes mais rapido que o tempo necessario para executar o BLASTX em todas as sequencias testadas. O quest tem outras aplicacoes, incluindo a determinacao do organismo de origem na nova abordagem genomica chamada de genomica ambiental (tambem chamada de metagenomica). 
Abstract

João Paulo Piazza

Papers

Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni

Identification and Genomic Characterization of a New Virus (Tymoviridae Family) Associated with Citrus Sudden Death Disease

New ways for automatic detection of contaminats in EST projects.

Uma metodologia para determinação do organismo de origem de sequencias de DNA com aplicação em projetos EST